Erratum: Accuracy of 68Ga-PSMA-11 PET/CT and multiparametric MRI for the detection of local tumor and lymph node metastases in early biochemical recurrence of prostate cancer.

[This corrects the article on p. 106 in vol. 10, PMID: 32419979.].

MR imaging of the airways.

The need for airway imaging is defined by the limited sensitivity of common clinical tests like spirometry, lung diffusion (DLCO) and blood gas analysis to early changes of peripheral airways and to inhomogeneous regional distribution of lung function deficits. Therefore, X-ray and computed tomography (CT) are frequently used to complement the standard tests.As an alternative, magnetic resonance imaging (MRI) offers radiation-free lung imaging, but at lower spatial resolution. Non-contrast enhanced MRI shows healthy airways down to the first subsegmental level/4th order (CT: eighth). Bronchiectasis can be identified by wall thickening and fluid accumulation. Smaller airways become visible, when altered by peribronchiolar inflammation or mucus retention (tree-in-bud sign).The strength of MRI is functional imaging. Dynamic, time-resolved MRI directly visualizes expiratory airway collapse down to the lobar level (CT: segmental level). Obstruction of even smaller airways becomes visible as air trapping on the expiratory scans. MRI with hyperpolarized noble gases (3He, 129Xe) directly shows the large airways and peripheral lung ventilation. Dynamic contrast-enhanced MRI (DCE MRI) indirectly shows airway dysfunction as perfusion deficits resulting from hypoxic vasoconstriction of the dependent lung volumes. Further promising scientific approaches such as non-contrast enhanced, ventilation-/perfusion-weighted MRI from periodic signal changes of respiration and blood flow are in development.In summary, MRI of the lungs and airways excels with its unique combination of morphologic and functional imaging capacities for research (e.g., in chronic obstructive lung disease or asthma) as well as for clinical imaging (e.g., in cystic fibrosis).

Diagnostic scope of 18F-PSMA-1007 PET/CT: comparison with multiparametric MRI and bone scintigraphy for the assessment of early prostate cancer recurrence.

The aim of this study was to compare the diagnostic tools-18F-PSMA-1007 positron emission tomography (PET/CT), magnetic resonance imaging (MRI) and bone scintigraphy for the evaluation of local recurrence, regional lymph nodes and bone metastases of recurrent prostate cancer (PCa). 28 PCa patients after radical prostatectomy and/or radiation therapy and with biochemical relapse were enrolled in this study. The evaluation of local recurrence and regional lymph node metastases was based on results of PET/CT and MRI. Local recurrent disease in 28 patients was detected by PET/CT in 36% (10/28) and by MRI in 32% (9/28) with sensitivity, specificity, accuracy of 90.9%, 100%, 96.4% and 81.8%, 100%, 92.9%, respectively (kappa 0.92, P<0.001). Nodal involvement was confirmed by PET/CT and MRI in 46% (13/28) and 25% (7/28) with sensitivity, specificity and accuracy for PET/CT 92.3%, 93.3%, 92.9% and for MRI-53.8%, 100%, 78.6%, respectively (kappa 0.57, P<0.001). The evaluation of skeletal metastases was based on PET/CT and bone scintigraphy. Bone metastases were seen on PET/CT and bone scintigraphy in 21% (6/28) and 20% (5/25) with sensitivity, specificity and accuracy of 100%; 91.7%; 92.9% and 50.0%; 85.7%; 80.0%, respectively (kappa 0.41, P<0.01). In conclusion, our comparative study demonstrates advantages of 18F-PSMA-1007 PET/CT compared to MRI and scintigraphy for the evaluation of recurrent prostate cancer. Both methods, 18F-PSMA-1007 PET/CT and MRI, detect local recurrence with high accuracy and excellent agreement, which may be attributed to the low urinary background clearance of 18F-PSMA-1007.

Accuracy of 68Ga-PSMA-11 PET/CT and multiparametric MRI for the detection of local tumor and lymph node metastases in early biochemical recurrence of prostate cancer.

Anatomical and functional imaging plays a decisive role for detection and staging, of prostate cancer both primarily and post-treatment. While multiparametric MRI offers anatomic imaging with excellent soft tissue contrast, hybrid imaging based on positron emission tomography in combination with computed tomography (PET/CT) contributes functional imaging capacities. Since 68Ga-PSMA-11 was expected to be more efficient than the prior Choline-based PET radiotracers, it was the aim of the study to evaluate the diagnostic performance of the 68Ga-PSMA-11 PET/CT and multiparametric MRI in patients with recurrent prostate cancer and low PSA levels. 32 out of a cohort of 128 prostate cancer patients with biochemical relapse were referred for 68Ga-PSMA-11 PET/CT, MRI and bone scintigraphy. According to the histopathologically or clinically defined reference standard all results were classified as true positive, false positive, true negative or false negative. Local recurrence was present in 11/32 patients, lymph node metastases - in 13/32 patients and, bone metastases - in 6/32 patients. Against the standard of reference, sensitivity, specificity and accuracy for local recurrence of PET/CT were 63.6 %; 73.7%; 77.8%, respectively. MRI reached 90.9%; 94.7%; 92.3%, respectively. For local lymph node metastases PET/CT - 83.3%; 80.0% and 90.6%, respectively. MRI - 41.7%; 94.4%; 72.0%, respectively. For evaluation of bone metastases in PET/CT - 83.3%; 92.0%; 71.0%, respectively. Bone scintigraphy - 50.0%; 84.0%; 77.4%, respectively. In conclusion, mpMRI offered the better diagnostic accuracy in the detection of local recurrence and while PSMA PET/CT was superior in the detection of distant and lymph node metastases.

Cost-effectiveness of lung MRI in lung cancer screening.

OBJECTIVES: Recent studies with lung MRI (MRI) have shown high sensitivity (Sn) and specificity (Sp) for lung nodule detection and characterization relative to low-dose CT (LDCT). Using this background data, we sought to compare the potential screening performance of MRI vs. LDCT using a Markov model of lung cancer screening. METHODS: We created a Markov cohort model of lung cancer screening which incorporated lung cancer incidence, progression, and mortality based on gender, age, and smoking burden. Sensitivity (Sn) and Sp for LDCT were taken from the MISCAN Lung Microsimulation and Sn/Sp for MRI was estimated from a published substudy of the German Lung Cancer Screening and Intervention Trial. Screening, work-up, and treatment costs were estimated from published data. Screening with MRI and LDCT was simulated for a cohort of male and female smokers (2 packs per day; 36 pack/years of smoking history) starting at age 60. We calculated the screening performance and cost-effectiveness of MRI screening and performed a sensitivity analysis on MRI Sn/Sp and cost. RESULTS: There was no difference in life expectancy between MRI and LDCT screening (males 13.28 vs. 13.29 life-years; females 14.22 vs. 14.22 life-years). MRI had a favorable cost-effectiveness ratio of $258,169 in men and $403,888 in women driven by fewer false-positive screens. On sensitivity analysis, MRI remained cost effective at screening costs < $396 dollars and Sp > 81%. CONCLUSIONS: In this Markov model of lung cancer screening, MRI has a near-equivalent life expectancy benefit and has superior cost-effectiveness relative to LDCT. KEY POINTS: • In this Markov model of lung cancer screening, there is no difference in mortality between yearly screening with MRI and low-dose CT. • Compared to low-dose CT, screening with MRI led to a reduction in false-positive studies from 26 to 2.8% in men and 26 to 2.6% in women. • Due to similar life-expectancy and reduced false-positive rate, we found a favorable cost-effectiveness ratio of $258,169 in men and $403,888 in women of MRI relative to low-dose CT.

Screening for lung cancer: Does MRI have a role?

While the inauguration of national low dose computed tomographic (LDCT) lung cancer screening programs has started in the USA, other countries remain undecided, awaiting the results of ongoing trials. The continuous technical development achieved by stronger gradients, parallel imaging and shorter echo time has made lung magnetic resonance imaging (MRI) an interesting alternative to CT. For the detection of solid lesions with lung MRI, experimental and clinical studies have shown a threshold size of 3-4mm for nodules, with detection rates of 60-90% for lesions of 5-8mm and close to 100% for lesions of 8mm or larger. From experimental work, the sensitivity for infiltrative, non-solid lesions would be expected to be similarly high as that for solid lesions, but the published data for the MRI detection of lepidic growth type adenocarcinoma is sparse. Moreover, biological features such as a longer T2 time of lung cancer tissue, tissue compliance and a more rapid uptake of contrast material compared to granulomatous diseases, in principle should allow for the multi-parametric characterization of lung pathology. Experience with the clinical use of lung MRI is growing. There are now standardized protocols which are easy to implement on current scanner hardware configurations. The image quality has become more robust and currently ongoing studies will help to further contribute experience with multi-center, multi-vendor and multi-platform implementation of this technology. All of the required prerequisites have now been achieved to allow for a dedicated prospective large scale MRI based lung cancer screening trial to investigate the outcomes from using MRI rather than CT for lung cancer screening. This is driven by the hypothesis that MRI would reach a similarly high sensitivity for the detection of early lung cancer with fewer false positive exams (better specificity) than LDCT. The purpose of this review article is to discuss the potential role of lung MRI for the early detection of lung cancer from a technical point of view and to discuss a few of the possible scenarios for lung cancer screening implementation using this imaging modality. There is little doubt that MRI could play a significant role in lung cancer screening, but how and when will depend on the threshold needed for positive screens (e.g. lesion volume and required diagnostic accuracy), cost-effectiveness and improved patient outcomes from a reduction in the need to follow up benign nodules. Potential applications range from lung MRI as the first choice screening modality to the role of an ad hoc on site test for the detailed evaluation of a subgroup of positive screening results.

PET/CT versus MRI for diagnosis, staging, and follow-up of lung cancer.

Positron emission tomography / computed tomography (PET/CT), with its metabolic data of (18) F-fluorodeoxyglucose (FDG) cellular uptake in addition to morphologic CT data, is an established technique for staging of lung cancer and has higher sensitivity and accuracy for lung nodule characterization than conventional approaches. Its strength extends outside the chest, with unknown metastases detected or suspected metastases excluded in a significant number of patients. Lastly, PET/CT is used in the assessment of therapy response. Magnetic resonance imaging (MRI) in the chest has been difficult to establish, but with the advent of new sequences is starting to become an increasingly useful alternative to conventional approaches. Diffusion-weighted MRI (DWI) is useful for distinguishing benign and malignant pulmonary nodules, has high sensitivity and specificity for nodal staging, and is helpful for evaluating an early response to systemic chemotherapy. Whole-body MRI/PET promises to contribute additional information with its higher soft-tissue contrast and much less radiation exposure than PET/CT and has become feasible for fast imaging and can be used for cancer staging in patients with a malignant condition.

CT fluoroscopy-guided lung biopsy with novel steerable biopsy canula: ex-vivo evaluation in ventilated porcine lung explants.

The purpose was to evaluate ex-vivo a prototype of a novel biopsy canula under CT fluoroscopy-guidance in ventilated porcine lung explants in respiratory motion simulations. Using an established chest phantom for porcine lung explants, n = 24 artificial lesions consisting of a fat-wax-Lipiodol mixture (approx. 70HU) were placed adjacent to sensible structures such as aorta, pericardium, diaphragm, bronchus and pulmonary artery. A piston pump connected to a reservoir beneath a flexible silicone reconstruction of a diaphragm simulated respiratory motion by rhythmic inflation and deflation of 1.5 L water. As biopsy device an 18-gauge prototype biopsy canula with a lancet-like, helically bended cutting edge was used. The artificial lesions were punctured under CT fluoroscopy-guidance (SOMATOM Sensation 64, Siemens, Erlangen, Germany; 30mAs/120 kV/5 mm slice thickness) implementing a dedicated protocol for CT fluoroscopy-guided lung biopsy. The mean-diameter of the artificial lesions was 8.3 +/- 2.6 mm, and the mean-distance of the phantom wall to the lesions was 54.1 +/- 13.5 mm. The mean-displacement of the lesions by respiratory motion was 14.1 +/- 4.0 mm. The mean-duration of CT fluoroscopy was 9.6 +/- 5.1 s. On a 4-point scale (1 = central; 2 = peripheral; 3 = marginal; 4 = off target), the mean-targeted precision was 1.9 +/- 0.9. No misplacement of the biopsy canula affecting adjacent structures could be detected. The novel steerable biopsy canula proved to be efficient in the ex-vivo set-up. The chest phantom enabling respiratory motion and the steerable biopsy canula offer a feasible ex-vivo system for evaluating and training CT fluoroscopy-guided lung biopsy adapted to respiratory motion.

4D-Imaging of the lung: reproducibility of lesion size and displacement on helical CT, MRI, and cone beam CT in a ventilated ex vivo system.

PURPOSE: Four-dimensional (4D) imaging is a key to motion-adapted radiotherapy of lung tumors. We evaluated in a ventilated ex vivo system how size and displacement of artificial pulmonary nodules are reproduced with helical 4D-CT, 4D-MRI, and linac-integrated cone beam CT (CBCT). METHODS AND MATERIALS: Four porcine lungs with 18 agarose nodules (mean diameters 1.3-1.9 cm), were ventilated inside a chest phantom at 8/min and subject to 4D-CT (collimation 24 x 1.2 mm, pitch 0.1, slice/increment 24 x 10(2)/1.5/0.8 mm, pitch 0.1, temporal resolution 0.5 s), 4D-MRI (echo-shared dynamic three-dimensional-flash; repetition/echo time 2.13/0.72 ms, voxel size 2.7 x 2.7 x 4.0 mm, temporal resolution 1.4 s) and linac-integrated 4D-CBCT (720 projections, 3-min rotation, temporal resolution approximately 1 s). Static CT without respiration served as control. Three observers recorded lesion size (RECIST-diameters x/y/z) and axial displacement. Interobserver- and interphase-variation coefficients (IO/IP VC) of measurements indicated reproducibility. RESULTS: Mean x/y/z lesion diameters in cm were equal on static and dynamic CT (1.88/1.87; 1.30/1.39; 1.71/1.73; p > 0.05), but appeared larger on MRI and CBCT (2.06/1.95 [p < 0.05 vs. CT]; 1.47/1.28 [MRI vs. CT/CBCT p < 0.05]; 1.86/1.83 [CT vs. CBCT p < 0.05]). Interobserver-VC for lesion sizes were 2.54-4.47% (CT), 2.29-4.48% (4D-CT); 5.44-6.22% (MRI) and 4.86-6.97% (CBCT). Interphase-VC for lesion sizes ranged from 2.28% (4D-CT) to 10.0% (CBCT). Mean displacement in cm decreased from static CT (1.65) to 4D-CT (1.40), CBCT (1.23) and MRI (1.16). CONCLUSIONS: Lesion sizes are exactly reproduced with 4D-CT but overestimated on 4D-MRI and CBCT with a larger variability due to limited temporal and spatial resolution. All 4D-modalities underestimate lesion displacement.

MRI of pulmonary nodules: technique and diagnostic value.

Chest wall invasion by a tumour and mediastinal masses are known to benefit from the superior soft tissue contrast of magnetic resonance imaging (MRI). However, helical computed tomography (CT) (i.e. with multiple row detector systems) remains the modality of choice to detect and follow lesions of the lung parenchyma. Since minimizing radiation exposure plays a minor role in oncologic patients, there are only few routine indications for which MRI of lung parenchyma is preferred to CT. This includes whole body MR imaging for staging or scientific studies with frequent follow-up examinations. MR-based lung imaging in this context was always considered as a weak point. Depending on the sequence technique and imaging conditions (i.e. ability to hold breath) the threshold for lung nodule detection with MRI using 1.5 T systems was estimated to be above 3-4 mm. The feasibility of lung MRI at 0.3-0.5 T and 3.0 T systems has been demonstrated. The clinical value of time-resolved lung nodule perfusion analysis cannot yet be determined, although the combination of perfusion characteristics with morphologic criteria contributes to estimate the integrity of a solitary lesion.

Respiratory-gated helical computed tomography of lung: reproducibility of small volumes in an ex vivo model.

PURPOSE: Motion-adapted radiotherapy with gated irradiation or tracking of tumor positions requires dedicated imaging techniques such as four-dimensional (4D) helical computed tomography (CT) for patient selection and treatment planning. The objective was to evaluate the reproducibility of spatial information for small objects on respiratory-gated 4D helical CT using computer-assisted volumetry of lung nodules in a ventilated ex vivo system. METHODS AND MATERIALS: Five porcine lungs were inflated inside a chest phantom and prepared with 55 artificial nodules (mean diameter, 8.4 mm +/- 1.8). The lungs were respirated by a flexible diaphragm and scanned with 40-row detector CT (collimation, 24 x 1.2 mm; pitch, 0.1; rotation time, 1 s; slice thickness, 1.5 mm; increment, 0.8 mm). The 4D-CT scans acquired during respiration (eight per minute) and reconstructed at 0-100% inspiration and equivalent static scans were scored for motion-related artifacts (0 or absent to 3 or relevant). The reproducibility of nodule volumetry (three readers) was assessed using the variation coefficient (VC). RESULTS: The mean volumes from the static and dynamic inspiratory scans were equal (364.9 and 360.8 mm3, respectively, p = 0.24). The static and dynamic end-expiratory volumes were slightly greater (371.9 and 369.7 mm3, respectively, p = 0.019). The VC for volumetry (static) was 3.1%, with no significant difference between 20 apical and 20 caudal nodules (2.6% and 3.5%, p = 0.25). In dynamic scans, the VC was greater (3.9%, p = 0.004; apical and caudal, 2.6% and 4.9%; p = 0.004), with a significant difference between static and dynamic in the 20 caudal nodules (3.5% and 4.9%, p = 0.015). This was consistent with greater motion-related artifacts and image noise at the diaphragm (p <0.05). The VC for interobserver variability was 0.6%. CONCLUSION: Residual motion-related artifacts had only minimal influence on volumetry of small solid lesions. This indicates a high reproducibility of spatial information for small objects in low pitch helical 4D-CT reconstructions.

Four-dimensional multislice helical CT of the lung: qualitative comparison of retrospectively gated and static images in an ex-vivo system.

PURPOSE: To analyse the image quality of retrospectively gated helical CT using controlled respiratory motion of porcine lung explants. MATERIALS AND METHODS: Five porcine lungs were examined inside a chest phantom. A silicone membrane was rhythmically inflated and deflated to simulate diaphragmatic respiration. Dynamic images (regular respiration at 8/min) and static scans (w/o respiration) at 0/25/50/75 and 100% of maximum inspiration were acquired with a 40-row detector CT scanner (rotation time 1s, pitch 0.1). Image quality on multi-planar reformations was evaluated by two observers. Partial projection artifacts, stepladder-artifacts and noise were compared for upper, middle and lower parts of the lung and different respiratory phases (scores 0-3 for absent, minimal, moderate and diagnostically relevant artifacts). RESULTS: Partial projection effects were limited to dynamic scans (mean score 1.33). Stepladder artifacts predominated in dynamic series compared to static series (mean score 0.55 versus 0.1; p<0.001). Image noise was not related to lung motion (mean scores 0.68-0.81). All artifacts predominated close to the diaphragm compared to the upper and middle parts of the lung (p<0.001 to p=0.02, respectively). Partial projection and stepladder artifacts were less in end-inspiration and end-expiration than within the respiration (p<0.001 and p=0.17, respectively). Diagnostically relevant artifacts were noted 9 times (9/9 close to diaphragm, 7/9 partial-projection). CONCLUSIONS: Even in ideal realistic conditions, helical 4D-CT produced tolerable artifacts which could be overcome by radiologists.

Therapy monitoring using dynamic MRI: analysis of lung motion and intrathoracic tumor mobility before and after radiotherapy.

A frequent side effect after radiotherapy of lung tumors is a decrease of pulmonary function accompanied by dyspnea due to developing lung fibrosis. The aim of this study was to monitor lung motion as a correlate of pulmonary function and intrathoracic tumor mobility before and after radiotherapy (RT) using dynamic MRI (dMRI). Thirty-five patients with stage I non-small-cell lung carcinoma were examined using dMRI (trueFISP; three images/s). Tumors were divided into T1 and T2 tumors of the upper, middle and lower lung region (LR). Maximum craniocaudal (CC) lung dimensions and tumor mobility in three dimensions were monitored. Vital capacity (VC) was measured and correlated using spirometry. Before RT, the maximum CC motion of the tumor-bearing hemithorax was 5.2 +/- 0.9 cm if the tumor was located in the lower LR (middle LR: 5.5 +/- 0.8 cm; upper LR: 6.0 +/- 0.6 cm). After RT, lung motion was significantly reduced in the lower LR (P < 0.05). Before RT, the maximum CC tumor mobility was significantly higher in tumors of the lower LR 2.5 +/- 0.6 vs. 2.0 +/- 0.3 cm (middle LR; P < 0.05) vs. 0.7 +/- 0.2 cm (upper LR; P < 0.01). After RT, tumor mobility was significantly reduced in the lower LR (P < 0.01) and in T2 tumor patients (P < 0.05). VC showed no significant changes. dMRI is capable of monitoring changes in lung motion that were not suspected from spirometry. This might make the treatment of side effects possible at a very early stage. Changes of lung motion and tumor mobility are highly dependent on the tumor localization and tumor diameter.